West Nile virus (WNV) capsid (C) protein was shown to enter the nucleus via importin-mediated pathway and induce apoptosis although the precise regulatory mechanisms for such events have remained elusive. In this study, it was shown that WNV C protein was phosphorylated by protein kinase C (PKC). PKC-mediated phosphorylation influenced nuclear trafficking of C protein by modulating the efficiency of C protein-importin-alpha binding. Combination of bio-informatics, site-directed mutagenesis, co-immunoprecipitation, immuno-fluorescence and mammalian two-hybrid analyses showed that phosphorylation at amino acid residues residing near (Ser83) or within (Ser99 and Thr100) the bipartite nuclear localization motif of WNV C protein was essential for efficient interaction between C protein and importin-alpha. In addition, phosphorylation of WNV C protein by PKC was shown to enhance its binding to HDM2 and could subsequently induce p53-dependent apoptosis. Collectively, this study highlighted that phosphorylation is an important post-translational modification required to execute the functions of C protein.
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http://dx.doi.org/10.1016/j.micinf.2010.04.005 | DOI Listing |
J Biol Chem
January 2025
Institute of Virology, Philipps University Marburg, Marburg, Germany. Electronic address:
Orthoflaviviruses are emerging arthropod-borne pathogens whose replication cycle is tightly linked to host lipid metabolism. Previous lipidomic studies demonstrated that infection with the closely related hepatitis C virus (HCV) changes the fatty acid (FA) profile of several lipid classes. Lipids in HCV-infected cells had more very long-chain and desaturated FAs and viral replication relied on functional FA elongation and desaturation.
View Article and Find Full Text PDFViruses
January 2025
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami/UHealth, Miami, FL 33136, USA.
Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy.
View Article and Find Full Text PDFViruses
December 2024
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, CA 92093-0657, USA.
Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral-host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development.
View Article and Find Full Text PDFPathogens
January 2025
Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia.
Neuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia. A total of 43 patients with confirmed flavivirus infection hospitalized from 2017 to 2023 were included in the study.
View Article and Find Full Text PDFFront Immunol
January 2025
Infectious Disease Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University of Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Due to their widespread geographic distribution and frequent outbreaks, mosquito-borne flaviviruses, such as DENV (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), and West Nile virus (WNV), are considered significant global public health threats and contribute to dramatic socioeconomic imbalances worldwide. The global prevalence of these viruses is largely driven by extensive international travels and ecological disruptions that create favorable conditions for the breeding of and species, the mosquito vectors responsible for the spread of these pathogens. Currently, vaccines are available for only DENV, YFV, and JEV, but these face several challenges, including safety concerns, lengthy production processes, and logistical difficulties in distribution, especially in resource-limited regions, highlighting the urgent need for innovative vaccine approaches.
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